In Reply: In response to Dr Trotter, our study
used a prospective nested case-control design, in which healthy controls were
selected at random using risk-set sampling (ie, controls were selected at
the time when diabetes cases occurred) and matched to the cases by age, race,
and fasting status. By design, the cases were expected to have higher prevalence
of diabetes risk factors, such as family history of diabetes, high body mass
index, lower physical activity levels, and higher levels of fasting insulin
and C-peptide, because these variables are established risk factors for type
2 diabetes. The question is whether the observed association between iron
overload and diabetes can be explained by these factors. We used 2 analytic
strategies to address this question. First, we adjusted for these covariates
in our multivariate analyses. Second, we conducted stratified analyses according
to levels of major diabetes risk factors. Both analyses indicated that iron
overload was a robust and independent risk factor for the development of type
2 diabetes in our cohort.